Exploratory Study on the Efficacy and Safety of Sintilimab Combined With Lenvatinib and HAIC for Neoadjuvant Therapy of Borderline Resectable Hepatocellular Carcinoma
This study is a single-center, randomized controlled exploratory Phase II clinical trial, aiming to assess the efficacy and safety of sintilimab combined with lenvatinib and HAIC for two cycles followed by surgery compared with direct surgery in patients with borderline resectable hepatocellular carcinoma. After signing the informed consent and meeting the inclusion and exclusion criteria, the eligible subjects were randomly divided into the experimental group and the control group: * Subjects in the experimental group received 200 mg of sintilimab by intravenous infusion on the first day of every 3 weeks. Lenvatinib 8 mg was orally administered once daily, combined with the HAIC-FOLFOX regimen. After two cycles, the patients' conditions were evaluated for surgery. * Subjects in the control group underwent surgery directly. Both groups of subjects received sintilimab monotherapy as adjuvant treatment for half a year (a total of 8 cycles) after surgery. The treatment was terminated if there was disease recurrence, death, intolerable toxicity, withdrawal of informed consent, initiation of new anti-tumor treatment, or other reasons stipulated in the protocol.
• Sign a written informed consent before the implementation of any trial-related procedures.
• Male or female, aged ≥18 years and ≤70 years.
• ECOG PS score of 0-2.
• Diagnosed with HCC according to the Diagnosis and Treatment Guidelines for Primary Liver Cancer in China (2019 Edition).
• CNLC stage IIIa, with vascular invasion but no extrahepatic metastasis.
• Child-Pugh score of A/B.
• Portal vein tumor thrombus is classified as type 1-2 according to the Japanese VP classification or type I-II according to the Program classification.
• No previous systemic anti-tumor treatment for hepatocellular carcinoma and eligible for R0 resection.
• Expected survival time \> 3 months.
⁃ At least one measurable lesion according to RECIST 1.1 or mRECIST criteria.
⁃ Adequate organ and bone marrow function, as follows:
‣ 1\) Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L; platelet count (PLT) ≥ 75×109/L; hemoglobin content (HGB) ≥ 9.0 g/dL.
‣ 2\) Liver function: serum total bilirubin (TBIL) ≤ 3×ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 5×ULN; serum albumin ≥ 28 g/L.
‣ 3\) Renal function: serum creatinine (Cr) ≤ 1.5×ULN or clearance of creatinine (CCr) ≥ 50 mL/min (Cockcroft-Gault formula); urine routine test shows urine protein \< 2+; for patients with urine protein ≥ 2+ at baseline, 24-hour urine collection is required and 24-hour urine protein quantification \< 1 g.
‣ 4\) Coagulation function: international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
‣ 12\. For patients with acute or chronic active hepatitis B or C, continuous antiviral treatment is required during the study period.
‣ 13\. For female subjects of childbearing age, a urine or serum pregnancy test must be negative within 3 days before the first administration of the study drug (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non-childbearing age females are defined as those who have been postmenopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy.
‣ 14\. If there is a risk of pregnancy, all subjects (regardless of gender) must use a contraceptive method with a failure rate of less than 1% throughout the treatment period until 120 days after the last administration of the study drug (or 180 days after the last administration of chemotherapy drugs). Expected survival time ≥ 12 weeks.